Unknown

Dataset Information

0

TLR3/TRIF signalling pathway regulates IL-32 and IFN-? secretion through activation of RIP-1 and TRAF in the human cornea.


ABSTRACT: Toll-like receptor-3 (TLR3) and RNA helicase retinoic-acid-inducible protein-1 (RIG-I) serve as cytoplasmic sensors for viral RNA components. In this study, we investigated how the TLR3 and RIG-I signalling pathway was stimulated by viral infection to produce interleukin (IL)-32-mediated pro-inflammatory cytokines and type I interferon in the corneal epithelium using Epstein-Barr virus (EBV)-infected human cornea epithelial cells (HCECs/EBV) as a model of viral keratitis. Increased TLR3 and RIG-I that are responded to EBV-encoded RNA 1 and 2 (EBER1 and EBER2) induced the secretion of IL-32-mediated pro-inflammatory cytokines and IFN-? through up-regulation of TRIF/TRAF family proteins or RIP-1. TRIF silencing or TLR3 inhibitors more efficiently inhibited sequential phosphorylation of TAK1, TBK1, NF-?B and IRFs to produce pro-inflammatory cytokines and IFN-? than RIG-I-siRNA transfection in HCECs/EBV. Blockade of RIP-1, which connects the TLR3 and RIG-I pathways, significantly blocked the TLR3/TRIF-mediated and RIG-I-mediated pro-inflammatory cytokines and IFN-? production in HCECs/EBV. These findings demonstrate that TLR3/TRIF-dependent signalling pathway against viral RNA might be a main target to control inflammation and anti-viral responses in the ocular surface.

SUBMITTER: Park GB 

PROVIDER: S-EPMC4420606 | BioStudies | 2015-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

2011-01-01 | S-EPMC3169542 | BioStudies
2009-01-01 | S-EPMC2683030 | BioStudies
2013-01-01 | S-EPMC3893785 | BioStudies
2020-01-01 | S-EPMC7232131 | BioStudies
1000-01-01 | S-EPMC3612606 | BioStudies
2010-01-01 | S-EPMC2973831 | BioStudies
1000-01-01 | S-EPMC3250173 | BioStudies
2014-01-01 | S-EPMC4054379 | BioStudies
2019-01-01 | S-EPMC6739404 | BioStudies
2018-01-01 | S-EPMC5860983 | BioStudies